一种逐步增长肽段的柔性多肽对接方案研究-生物化学与分子生物学专业论文.docx

一种逐步增长肽段的柔性多肽对接方案The Study of A Flexible Peptide Docking Approach via Peptide Fragment GrowthAbstractThe peptide bmdmg on protein plays an important role in innate immunity and signaling pathways，relevant to some common diseases such as cancer and turnout．The theoretical study of protein．peptide interactions Can provide information at molecular level to help understand the details of these complex biological processes，in order to regulate the protein。peptlde interactions and assist the treatments of the related diseases．In addition，investigating theprotein-peptide docking process can help design novel peptide drugs．The peptide flexibility causes the computational difjficulty when using the conventional docking tools．Here，we ore going to propose a flexible docking approach to exam the dockingof C1．CATH2 on the interface of TLR4-MD2． This approach contains the following steps：1)Homology modeling and ab initio modeling to obtain a series of candidate Q-helix structures．2) Each c【．helix is used as the initial structure to generate 3600 conformations using ZDock， leading to the top 600 conformations with favorable scores．3)The top 600 conformations weresubject to RosettaDock redock plus consensus scoring for generating the best conformation．4) The RosettaDock semi．flexible docking was used to optimize the starting structure．5)Energy minimization was performed using amber to further optimize the structure．6)The peptide fragment Was grown gradually to the full peptide using our inhouse tools and Amberminimization． Molecular dynamics simulations and binding free energy analysis were used todetermine the accuracy and stability of the docked conformations．Finally，according to thebinding free energy，Van der Waals，electrostatic interactions and SO on，four possible modes have been obtained for the TLIH．MD2／C1一CATH2 binding．This article provides a comprehensive flexible peptide growth approach for the study ofthe proteins．peptides docking process．It is efficient，practicable and